Analisi in tutto il cervello dell'espressione delle reti perineuronali in topi mutanti Fmr1 e di controllo

Fragile X syndrome (FXS) is the most common cause of intellectual disability and autism spectrum disorder. In most cases, FXS is caused by epigenetic inactivation of the fragile X mental retardation 1 (Fmr1) gene. Mice knockout for the Fmr1 gene (Fmr1KO mice) exhibit the main symptoms of FXS and recently a disorganization of perineuronal nets (PNNs) causing sensory hypersensitivity was recently demonstrated in this model. PNNs are specialized forms of extracellular matrix (ECM), which assemble at the closure of developmental critical periods of plasticity and control synaptic connectivity and functions in the central nervous system. Accordingly, PNN expression is altered in various neuropsychiatric disorders, and converging evidence show that PNN manipulation may rescue physiological and behavioral deficits.Based on these data, the main objective of this work is to conduct a brain-wide analysis of PNNs in Fmr1KO mice compared to wild type controls. Indeed, little is known yet of FXS-dependent PNN alterations affecting activity and plasticity of brain areas controlling different physiological and behavioral functions. To this aim here we have developed a customized method for brain wide 3D reconstruction and analysis of histologically stained serial sections (3DVR, 3D virtual reconstruction, schematized in a graphical abstract below) followed by high-throughput imaging analysis.